The clinical condition of sarcopenia, a hallmark of aging, is characterized by a loss of muscle mass and function, which is more pronounced in Type II (fast-twitch) muscle fibers. Healthy Type II muscle fibers are 5-6 fold more powerful than Type I (slow-twitch) muscle fibers and critical for whole muscle performance (i.e. prevention of falls). To date, interventions to improve the function and health profile of Type II muscle fibers in old (>70 y) adults have been largely unsuccessful. The main goal of this research will be to implement three novel approaches to further our knowledge of the etiology of sarcopenia: 1) complement our single muscle fiber contractile function measurements with new and innovative methods to study protein synthesis, protein signaling, and gene expression (including microarray) in Type I and Type II muscle fibers with aging. This fiber type specific information will advance our understanding of the myocellular basis of sarcopenia since our knowledge about these physiological processes is limited to muscle homogenate preparations that contain a mixture of fiber types;2) include a cohort of life-long exercisers;and 3) include a cohort of older individuals who became consistent exercisers later in life (late-life exercisers). These three combined strategies will add significant insight into the influence that regular physical activity throughout the lifespan has on myocellular health as a preventative therapy, particularly for the Type II muscle fibers. There are little data on life-long and late-life exercisers and no data on the skeletal muscle health of these adults in a fiber type specific manner. We will recruit 80 volunteers that will be equally divided and gender balanced into four groups (n=20) that include old life-long exercisers (70-79 y), old late-life exercisers (70-79 y), old life-long non-exercising adults (70-79 y), and young non-exercising adults (20-29 y). Our general hypotheses are two-fold: 1) Type II muscle fibers from old life-long exercisers, old late-life exercisers, and young non-exercisers will be healthier than Type II muscle fibers from old non-exercising adults in the basal state and 2) Type II muscle fibers from old life- long exercisers, old late-life exercisers, and young non-exercisers will have a robust anabolic response to resistance exercise, while Type II muscle fibers from old non-exercising adults will have a blunted anabolic response to exercise. We have identified significant knowledge gaps in human skeletal muscle that are fiber type specific (Type I vs. Type II) regarding basal muscle health, acute exercise response and chronic life-long and late-life exercise. The investigative team is in a unique position to provide new information on life-long and late-life exercise and muscle fiber type specific functional, metabolic, protein, and genetic measurements. The Human Performance Laboratory has the longest running community based supervised exercise program in the United States that began during the 1960's exercise boom and has tracked the physiological, health, and exercise profiles of >5,500 adults. The knowledge gained from this research will be crosscutting for numerous scientific disciplines and health care providers involved with skeletal muscle health and preventative medicine. PUBLIC HEALTH RELEVANCE: This research program will provide new information in the area of skeletal muscle health with aging and exercise. The relevance and broad scope of our proposal is highlighted by the fact that all 19 NIH Institutes are currently funding research related to skeletal muscle in health and disease. The knowledge gained will be useful for scientists, clinicians, and health-care providers involved with skeletal muscle health and help guide therapeutic interventions for skeletal muscle wasting.